PROJECT SUMMARY/ABSTRACT Early brain injury, caused by stroke, is one of the primary causes of cerebral palsy. Individual lifetime costs of care for an individual with cerebral palsy are estimated at over $1M. Understanding the manner in which the brain recovers after early brain injury, and the impact on resultant motor function, will allow future development of targeted and effective rehabilitation interventions in this uniquely neuroplastic infant population. The first year of life post-injury represents a ?window of opportunity? to advance our knowledge of the changes in brain organization and excitability that contribute to motor function. Non-invasive brain stimulation can assess brain excitability and identify patterns of connectivity, or circuitry in the brain, especially as the brain both recovers and develops after a perinatal injury. Brain stimulation can be used therefore to characterize the excitability profiles of the cortical regions contributing to motor output and the circuitry of the descending corticospinal tract originating from these regions. Stimulation can serve as a unique tool to investigate recovery from brain injury complementing current neuroimaging and motor function assessments to predict outcomes. We propose to use one form of non-invasive brain stimulation, transcranial magnetic stimulation (TMS), to assess the excitability and circuitry of motor cortical areas in infants with early brain injury due to stroke. To complement this assessment, we will create individualized computational models of the TMS-induced electric field distribution in the infant brain using individual structural brain anatomy obtained through magnetic resonance imaging. For both infants with perinatal brain injury and age-matched typically-developing controls, we will create complementary computational models of TMS-induced electric fields in each hemisphere, based on individual neuroanatomy obtained from MRI. This combined approach will provide critical information about the structures and pathways activated by TMS, and offer insight into potential targets for future non-invasive brain stimulation interventions. The results from this proposed in this R21 will advance our understanding of infant brain development after perinatal injury by integrating TMS assessment and computational models to predict not only the impact of the stroke on developing motor circuitry but also the response to brain stimulation. We will integrate our findings in future studies comparing excitability and circuitry as variables that may contribute to motor outcomes. By integrating validated computational models of TMS-induced electric fields, we can use individualized anatomical targets for future neuromodulation studies in infants with defined circuitry patterns and develop tailored interventions to improve motor function in infants with early brain injury.